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Biomedicine & Pharmacotherapy =... Sep 2023Breast cancer is a leadingcause of cancer-related deaths in women globally, with triple-negative breast cancer (TNBC) being an aggressive subtype that lacks targeted... (Review)
Review
Breast cancer is a leadingcause of cancer-related deaths in women globally, with triple-negative breast cancer (TNBC) being an aggressive subtype that lacks targeted therapies and is associated with a poor prognosis. Polyphenols, naturally occurring compounds in plants, have been investigated as a potential therapeutic strategy for TNBC. This review provides an overview of the anticancer effects of polyphenols in TNBC and their mechanisms of action. Several polyphenols, including resveratrol, quercetin, kaempferol, genistein, epigallocatechin-3-gallate, apigenin, fisetin, hesperetin and luteolin, have been shown to inhibit TNBC cell proliferation, induce cell cycle arrest, promote apoptosis, and suppress migration/invasion in preclinical models. The molecular mechanisms underlying their anticancer effects involve the modulation of several signalling pathways, such as PI3K/Akt, MAPK, STATT, and NF-κB pathways. Polyphenols also exhibit synergistic effects with chemotherapy drugs, making them promising candidates for combination therapy. The review also highlights clinical trials investigating the potential use of polyphenols, individually or in combination therapy, against breast cancer. This review deepens the under-standing of the mechanism of action of respective polyphenols and provides valuable insights into the potential use of polyphenols as a therapeutic strategy for TNBC, and lays the groundwork for future research in this area.
Topics: Female; Humans; Triple Negative Breast Neoplasms; Polyphenols; Phosphatidylinositol 3-Kinases; Apoptosis; Cell Cycle Checkpoints; Cell Proliferation; Cell Line, Tumor
PubMed: 37481930
DOI: 10.1016/j.biopha.2023.115170 -
Metabolism: Clinical and Experimental Aug 2023The capacity of a polyphenol-enriched diet to modulate the epigenome in vivo is partly unknown. Given the beneficial metabolic effects of a Mediterranean (MED) diet... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The capacity of a polyphenol-enriched diet to modulate the epigenome in vivo is partly unknown. Given the beneficial metabolic effects of a Mediterranean (MED) diet enriched in polyphenols and reduced in red/processed meat (green-MED), as previously been proven by the 18-month DIRECT PLUS randomized controlled trial, we analyzed the effects of the green-MED diet on methylome and transcriptome levels to highlight molecular mechanisms underlying the observed metabolic improvements.
METHODS
Our study included 260 participants (baseline BMI = 31.2 kg/m, age = 5 years) of the DIRECT PLUS trial, initially randomized to one of the intervention arms: A. healthy dietary guidelines (HDG), B. MED (440 mg polyphenols additionally provided by walnuts), C. green-MED (1240 mg polyphenols additionally provided by walnuts, green tea, and Mankai: green duckweed shake). Blood methylome and transcriptome of all study subjects were analyzed at baseline and after completing the 18-month intervention using Illumina EPIC and RNA sequencing technologies.
RESULTS
A total of 1573 differentially methylated regions (DMRs; false discovery rate (FDR) < 5 %) were found in the green-MED compared to the MED (177) and HDG (377) diet participants. This corresponded to 1753 differentially expressed genes (DEGs; FDR < 5 %) in the green-MED intervention compared to MED (7) and HDG (738). Consistently, the highest number (6 %) of epigenetic modulating genes was transcriptionally changed in subjects participating in the green-MED intervention. Weighted cluster network analysis relating transcriptional and phenotype changes among participants subjected to the green-MED intervention identified candidate genes associated with serum-folic acid change (all P < 1 × 10) and highlighted one module including the KIR3DS1 locus, being negatively associated with the polyphenol changes (e.g. P < 1 × 10), but positively associated with the MRI-assessed superficial subcutaneous adipose area-, weight- and waist circumference- 18-month change (all P < 0.05). Among others, this module included the DMR gene Cystathionine Beta-Synthase, playing a major role in homocysteine reduction.
CONCLUSIONS
The green-MED high polyphenol diet, rich in green tea and Mankai, renders a high capacity to regulate an individual's epigenome. Our findings suggest epigenetic key drivers such as folate and green diet marker to mediate this capacity and indicate a direct effect of dietary polyphenols on the one‑carbon metabolism.
Topics: Humans; Diet, Mediterranean; Polyphenols; Diet; Obesity; Tea; Epigenesis, Genetic
PubMed: 37236302
DOI: 10.1016/j.metabol.2023.155594 -
Pharmacological Research Jul 2023Polyphenols, also known as phenolic compounds, are chemical substances containing aromatic rings as well as at least two hydroxyl groups. Natural phenolic compounds... (Review)
Review
Polyphenols, also known as phenolic compounds, are chemical substances containing aromatic rings as well as at least two hydroxyl groups. Natural phenolic compounds exist widely in plants, which protect plants from ultraviolet radiation and other insults. Phenolic compounds have superior pharmacological and nutritional properties (antimicrobial, antibacterial, antiviral, anti-sclerosis, antioxidant, and anti-inflammatory activities), which have been paid more and more attention by the scientific community. Phenols can protect key cellular components from reactive free radical damage, which is mainly due to their property to activate antioxidant enzymes and alleviate oxidative stress and inflammation. It can also inhibit or isolate reactive oxygen species and transfer electrons to free radicals, thereby avoiding cell damage. It has a regulatory role in glucose metabolism, which has a promising prospect in the prevention and intervention of diabetes. It also prevents cardiovascular disease by regulating blood pressure and blood lipids. Polyphenols can inhibit cell proliferation by affecting Erk1/2, CDK, and PI3K/Akt signaling pathways. Polyphenols can function as enhancers of intrinsic defense systems, including superoxide dismutase (SOD) and glutathione peroxidase (GPX). Simultaneously, they can modulate multiple proteins and transcription factors, making them promising candidates in the investigation of anti-cancer medications. This review focuses on multiple aspects of phenolic substances, including their natural origins, production process, disinfection activity, oxidative and anti-inflammatory functions, and the effects of different phenolic substances on tumors.
Topics: Humans; Antioxidants; Phosphatidylinositol 3-Kinases; Ultraviolet Rays; Oxidative Stress; Phenols; Neoplasms; Polyphenols; Free Radicals; Inflammation; Anti-Inflammatory Agents
PubMed: 37271425
DOI: 10.1016/j.phrs.2023.106812 -
Molecules (Basel, Switzerland) Dec 2023Fermented dairy products (e.g., yogurt, kefir, and buttermilk) are significant in the dairy industry. They are less immunoreactive than the raw materials from which they... (Review)
Review
Fermented dairy products (e.g., yogurt, kefir, and buttermilk) are significant in the dairy industry. They are less immunoreactive than the raw materials from which they are derived. The attractiveness of these products is based on their bioactivity and properties that induce immune or anti-inflammatory processes. In the search for new solutions, plant raw materials with beneficial effects have been combined to multiply their effects or obtain new properties. Polyphenols (e.g., flavonoids, phenolic acids, lignans, and stilbenes) are present in fruit and vegetables, but also in coffee, tea, or wine. They reduce the risk of chronic diseases, such as cancer, diabetes, or inflammation. Hence, it is becoming valuable to combine dairy proteins with polyphenols, of which epigallocatechin-3-gallate (EGCG) and chlorogenic acid (CGA) show a particular predisposition to bind to milk proteins (e.g., α-lactalbumin β-lactoglobulin, αs1-casein, and κ-casein). Reducing the allergenicity of milk proteins by combining them with polyphenols is an essential issue. As potential 'metabolic prebiotics', they also contribute to stimulating the growth of beneficial bacteria and inhibiting pathogenic bacteria in the human gastrointestinal tract. In silico methods, mainly docking, assess the new structures of conjugates and the consequences of the interactions that are formed between proteins and polyphenols, as well as to predict their action in the body.
Topics: Humans; Phenols; Polyphenols; Flavonoids; Cultured Milk Products; Milk Proteins
PubMed: 38138571
DOI: 10.3390/molecules28248081 -
Frontiers in Endocrinology 2023The aim was to conduct a systematic review and meta-analysis for assessing the effectiveness and safety of dietary polyphenol curcumin supplement on metabolic,... (Meta-Analysis)
Meta-Analysis Review
Effects of dietary polyphenol curcumin supplementation on metabolic, inflammatory, and oxidative stress indices in patients with metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
The aim was to conduct a systematic review and meta-analysis for assessing the effectiveness and safety of dietary polyphenol curcumin supplement on metabolic, inflammatory, and oxidative stress indices in patients with metabolic syndrome (MetS).
METHODS
A comprehensive search for clinical trials was conducted in the following scientific databases: PubMed, SCOPUS, Cochrane Library, EMBASE, Web of Science, and China Biological Medicine. Randomized controlled trials (RCTs) evaluating the efficacy and safety of curcumin supplement for MetS were identified. A random-effects meta-analysis was performed using inverse variance, and efficacy was expressed as mean difference (MD) with 95% confidence interval (CI). The metabolic syndrome markers that were evaluated in the present study included waist circumference (WC), fasting blood sugar (FBS), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), tumor necrosis factor-a (TNF-a), interleukin 6 (IL-6), C-reactive protein (CRP), ultrasensitive c-reactive protein (hsCRP), and malondialdehyde (MDA). By employing the Cochrane tool, RCTs were assessed for bias risk.
RESULTS
A total of 785 participants from 13 RCTs were included, with intervention durations ranging from 4 to 12 weeks. Compared with the control group, the curcumin group had positive effects on WC (MD = -2.16, 95% CI: -3.78 to -0.54, = 0.009, seven studies), FBS (MD = -8.6, 95% CI: -15.45 to -1.75, = 0.01, nine studies), DBP (MD = -2.8, 95% CI: -4.53 to - 1.06, = 0.002, five studies), HDL-C (MD = 4.98, 95% CI: 2.58 to 7.38, < 0.0001, eight studies), TNF-a (MD = -12.97, 95% CI: -18.37 to -7.57, < 0.00001, two studies), CRP (MD = - 1.24, 95% CI: -1.71 to -0.77, < 0.00001, two studies), and MDA (MD = -2.35, 95% CI: -4.47 to -0.24, = 0.03, three studies). These improvements were statistically significant. Meanwhile, there was no significant improvement in SBP (MD = -4.82, 95% CI: -9.98 to 0.35, = 0.07, six studies), TG (MD = 1.28, 95% CI: -3.75 to 6.30, = 0.62, eight studies), IL-6 (MD = -1.5, 95% CI: -3.97 to 0.97, = 0.23, two studies), or hsCRP (MD = -1.10, 95% CI: -4.35 to 2.16, < 0.51, two studies). FBS, SBP, HDL-C, IL-6, CRP, hsCRP, and MDA had a relatively high heterogeneity.
CONCLUSION
Curcumin exhibited promising potential in enhancing markers associated with metabolic syndrome, including inflammation. However, additional studies are required to confirm such findings since the included evidence is limited and has a relatively high heterogeneity.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42022362553.
Topics: Randomized Controlled Trials as Topic; Curcumin; Dietary Supplements; Metabolic Syndrome; Oxidative Stress; Polyphenols; Inflammation; Humans; Curcuma
PubMed: 37522129
DOI: 10.3389/fendo.2023.1216708 -
Nutrients Jul 2023Green tea polyphenols have numerous functions including antioxidation and modulation of various cellular proteins and are thus beneficial against metabolic diseases... (Review)
Review
Green tea polyphenols have numerous functions including antioxidation and modulation of various cellular proteins and are thus beneficial against metabolic diseases including obesity, type 2 diabetes, cardiovascular and non-alcoholic fatty liver diseases, and their comorbidities. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea and is attributed to antioxidant and free radical scavenging activities, and the likelihood of targeting multiple metabolic pathways. It has been shown to exhibit anti-obesity, anti-inflammatory, anti-diabetic, anti-arteriosclerotic, and weight-reducing effects in humans. Worldwide, the incidences of metabolic diseases have been escalating across all age groups in modern society. Therefore, EGCG is being increasingly investigated to address the problems. This review presents the current updates on the effects of EGCG on metabolic diseases, and highlights evidence related to its safety. Collectively, this review brings more evidence for therapeutic application and further studies on EGCG and its derivatives to alleviate metabolic diseases and non-alcoholic fatty liver diseases.
Topics: Humans; Tea; Diabetes Mellitus, Type 2; Non-alcoholic Fatty Liver Disease; Catechin; Obesity; Antioxidants; Polyphenols; Metabolic Diseases
PubMed: 37447347
DOI: 10.3390/nu15133022 -
Biomedicine & Pharmacotherapy =... Nov 2023Blood retinal barrier (BRB) damage is an important pathogenesis of diabetic retinopathy, and alleviating BRB damage has become a key target for DR treatment. We...
Blood retinal barrier (BRB) damage is an important pathogenesis of diabetic retinopathy, and alleviating BRB damage has become a key target for DR treatment. We previously found that Lycopene seed polyphenols (LSP) maintained BRB integrity by inhibiting NLRP3 inflammasome-mediated inflammation. However, it is still unknown whether LSP inhibits retinal neovascularization with abnormal capillaries and its mechanism of action. Here, we employed db/db mice and hRECs to find that LSP increases the level of glycolipid metabolism, maintains the morphology of retinal endothelial cells and inhibits acellular capillary neogenesis. Mechanistic studies revealed that LSP inhibits the NLRP3 inflammasome, reduces cell apoptosis in retinal tissue, increases tight junction protein (TJ) expression, and reduces vascular endothelial growth factor (VEGF) and Ve-Cadherin in vivo and in vitro. Collectively, this study finds that LSP inhibits inflammation and angiogenesis to improve BRB function to ameliorate DR.
Topics: Mice; Animals; Inflammasomes; Litchi; Polyphenols; Endothelial Cells; NLR Family, Pyrin Domain-Containing 3 Protein; Vascular Endothelial Growth Factor A; Diabetic Retinopathy; Inflammation; Apoptosis
PubMed: 37703661
DOI: 10.1016/j.biopha.2023.115478 -
Cancer Metastasis Reviews Mar 2024Despite tremendous medical treatment successes, colorectal cancer (CRC) remains a leading cause of cancer deaths worldwide. Chemotherapy as monotherapy can lead to... (Review)
Review
Despite tremendous medical treatment successes, colorectal cancer (CRC) remains a leading cause of cancer deaths worldwide. Chemotherapy as monotherapy can lead to significant side effects and chemoresistance that can be linked to several resistance-activating biological processes, including an increase in inflammation, cellular plasticity, multidrug resistance (MDR), inhibition of the sentinel gene p53, and apoptosis. As a consequence, tumor cells can escape the effectiveness of chemotherapeutic agents. This underscores the need for cross-target therapeutic approaches that are not only pharmacologically safe but also modulate multiple potent signaling pathways and sensitize cancer cells to overcome resistance to standard drugs. In recent years, scientists have been searching for natural compounds that can be used as chemosensitizers in addition to conventional medications for the synergistic treatment of CRC. Resveratrol, a natural polyphenolic phytoalexin found in various fruits and vegetables such as peanuts, berries, and red grapes, is one of the most effective natural chemopreventive agents. Abundant in vitro and in vivo studies have shown that resveratrol, in interaction with standard drugs, is an effective chemosensitizer for CRC cells to chemotherapeutic agents and thus prevents drug resistance by modulating multiple pathways, including transcription factors, epithelial-to-mesenchymal transition-plasticity, proliferation, metastasis, angiogenesis, cell cycle, and apoptosis. The ability of resveratrol to modify multiple subcellular pathways that may suppress cancer cell plasticity and reversal of chemoresistance are critical parameters for understanding its anti-cancer effects. In this review, we focus on the chemosensitizing properties of resveratrol in CRC and, thus, its potential importance as an additive to ongoing treatments.
Topics: Humans; Resveratrol; Signal Transduction; Transcription Factors; Anticarcinogenic Agents; Colorectal Neoplasms; Stilbenes
PubMed: 37507626
DOI: 10.1007/s10555-023-10126-x -
Biosensors Jul 2023Nanomedicine has provided cutting-edge technologies and innovative methods for modern biomedical research, offering unprecedented opportunities to tackle crucial... (Review)
Review
Nanomedicine has provided cutting-edge technologies and innovative methods for modern biomedical research, offering unprecedented opportunities to tackle crucial biomedical issues. Nanomaterials with unique structures and properties can integrate multiple functions to achieve more precise diagnosis and treatment, making up for the shortcomings of traditional treatment methods. Among them, metal-polyphenol coordination polymers (MPCPs), composed of metal ions and phenolic ligands, are considered as ideal nanoplatforms for disease diagnosis and treatment. Recently, MPCPs have been extensively investigated in the field of biomedicine due to their facile synthesis, adjustable structures, and excellent biocompatibility, as well as pH-responsiveness. In this review, the classification of various MPCPs and their fabrication strategies are firstly summarized. Then, their significant achievements in the biomedical field such as biosensing, drug delivery, bioimaging, tumor therapy, and antibacterial applications are highlighted. Finally, the main limitations and outlooks regarding MPCPs are discussed.
Topics: Polyphenols; Phenols; Anti-Bacterial Agents; Metals; Polymers
PubMed: 37622862
DOI: 10.3390/bios13080776 -
Biomedicine & Pharmacotherapy =... Dec 2023Pericyte dysfunction and loss contribute substantially to the destabilization and rupture of atherosclerotic plaques. Protocatechuic aldehyde (PCAD), a natural...
Pericyte dysfunction and loss contribute substantially to the destabilization and rupture of atherosclerotic plaques. Protocatechuic aldehyde (PCAD), a natural polyphenol, exerts anti-atherosclerotic effects. However, the effects and mechanisms of this polyphenol on pericyte recruitment, coverage, and pericyte function remain unknown. We here treated apolipoprotein E-deficient mice having high-fat diet-induced atherosclerosis with PCAD. PCAD achieved therapeutic effects similar to rosuvastatin in lowering lipid levels and thus preventing atherosclerosis progression. With PCAD administration, plaque phenotype exhibited higher stability with markedly reduced lesion vulnerability, which is characterized by reduced lipid content and macrophage accumulation, and a consequent increase in collagen deposition. PCAD therapy increased pericyte coverage in the plaques, reduced VEGF-A production, and inhibited intraplaque neovascularization. PCAD promoted pericyte proliferation, adhesion, and migration to mitigate ox-LDL-induced pericyte dysfunction, which thus maintained the capillary network structure and stability. Furthermore, TGFBR1 silencing partially reversed the protective effect exerted by PCAD on human microvascular pericytes. PCAD increased pericyte coverage and impeded ox-LDL-induced damages through TGF-β1/TGFBR1/Smad2/3 signaling. All these novel findings indicated that PCAD increases pericyte coverage and alleviates pericyte damage to improve the stability of atherosclerotic plaques, which is accomplished by regulating TGF-β1/TGFBR1/Smad2/3 signaling in pericytes.
Topics: Animals; Mice; Humans; Plaque, Atherosclerotic; Pericytes; Transforming Growth Factor beta1; Receptor, Transforming Growth Factor-beta Type I; Atherosclerosis; Lipids; Polyphenols
PubMed: 37871558
DOI: 10.1016/j.biopha.2023.115742